Responses of DNA mismatch repair proteins to a stable G-quadruplex embedded into a DNA duplex structureстатьяЭлектронная публикация
Статья опубликована в высокорейтинговом журнале
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Дата последнего поиска статьи во внешних источниках: 8 января 2021 г.
Аннотация:DNA mismatch repair (MMR) plays a crucial role in the maintenance of genomic stability.The main MMR protein, MutS, was recently shown to recognize the G-quadruplex (G4) DNAstructures, which, along with regulatory functions, have a negative impact on genome integrity. Here, we studied the eect of G4 on the DNA-binding activity of MutS from Rhodobacter sphaeroides (methyl-independent MMR) in comparison with MutS from Escherichia coli (methyl-directed MMR)and evaluated the influence of a G4 on the functioning of other proteins involved in the initial steps of MMR. For this purpose, a new DNA construct was designed containing a biologically relevantintramolecular stable G4 structure flanked by double-stranded regions with the set of DNA sites required for MMR initiation. The secondary structure of this model was examined using NMR spectroscopy, chemical probing, fluorescent indicators, circular dichroism, and UV spectroscopy. The results unambiguously showed that the d(GGGT)4 motif, when embedded in a double-stranded context, adopts a G4 structure of a parallel topology. Despite strong binding anities of MutS and MutL for a G4, the latter is not recognized by E. coli MMR as a signal for repair, but does not prevent MMR processing when a G4 and G/T mismatch are in close proximity.